Biological assays are often performed in high-throughput systems to screen a large number of different compounds for their effect on a biological system, e.g., to screen a plurality of potential enzyme inhibitors. Many of these assays, e.g., enzyme assays, are performed in microfluidic devices as described, e.g., in a number of issued patents and published PCT applications. For example, microfluidic methods of performing biological assays in microfluidic systems have been developed, such as those described by the pioneering applications of Parce et al., “High Throughput Screening Assay Systems in Microscale Fluidic Devices” WO 98/00231 and in Knapp et al., “Closed Loop Biochemical Analyzers” (WO 98/45481).
Materials are typically transported through microfluidic devices by the application of pressure or electrokinetic forces to the channels of the device. The timing of reactions, e.g., in enzymatic reactions, is important for determining reaction kinetics and for making comparisons between various samples. Therefore, a variety of methods have been developed to monitor and control fluid flow in microfluidic systems.
For example, U.S. Pat. No. 5,800,690, by Chow, provides various power supplies, such as time-multiplexed power supplies, to vary the voltage in a microfluidic systems and control fluid movement. Published PCT application WO 98/56956, by Kopf-Sill at al., provides methods of correcting for variable velocity by flowing zwitterions through microfluidic systems. Channel dimensions and configurations have also been varied to provide control over fluid movement in microfluidic channels, such as in U.S. Pat. No. 5,842,787 by Kopf-Sill et al., and in U.S. Ser. No. 60/150,670 and U.S. Ser. No. 09/645,104, filed Aug. 23, 2000, by Kopf-Sill et al., entitled “Dilutions in High Throughput Systems with a Single Vacuum Source.” In “Method and Apparatus for Continuous Liquid Flow in Microscale Channels Using Pressure Injection, Wicking and Electrokinetic Injection,” by Alajoki et al., U.S. Ser. No. 09/245,627, filed Feb. 5, 1999, pressure injections and wicking methods for providing continuous flow are described and U.S. Pat. No. 6,001,231, by Kopf-Sill, describes methods of measuring a flow rate in a microfluidic channel.
The present invention provides improved methods and systems for monitoring and controlling flow rates in microfluidic systems. The methods and systems of the present invention provide these features and many others that will be apparent upon complete review of the following disclosure.